Skip to main content
Top
Published in: Documenta Ophthalmologica 3/2014

01-06-2014 | Original Research Article

Contribution of retinal ganglion cells to the mouse electroretinogram

Authors: Benjamin J. Smith, Xu Wang, Balwantray C. Chauhan, Patrice D. Côté, François Tremblay

Published in: Documenta Ophthalmologica | Issue 3/2014

Login to get access

Abstract

Purpose

To quantify the direct contribution of retinal ganglion cells (RGCs) on individual components of the mouse electroretinogram (ERG).

Methods

Dark- and light-adapted ERGs from mice 8 to 12 weeks after optic nerve transection (ONTx, n = 14) were analyzed through stimulus response curves for a- and b-waves, oscillatory potentials (OPs), positive and negative scotopic threshold response (p/n STR), and the photopic negative response (PhNR) and compared with unoperated and sham-operated controls, as well as to eyes treated with 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX).

Results

We confirmed in mice that CNQX intravitreal injection reduced the scotopic a-wave amplitude at high flash strength, confirming a post-receptoral contribution to the a-wave. We found that ONTx, which is more specific to RGCs, did not affect the a-wave amplitude and implicit time in either photopic or scotopic conditions while the b-wave was reduced. Both the pSTR and nSTR components were reduced in amplitude, with the balance between the two components resulting in a shortening of the nSTR peak implicit time. On the other hand, amplitude of the PhNR was increased while the OPs were minimally affected.

Conclusion

With an intact a-wave demonstrated following ONTx, we find that the most robust indicators of RGC function in the mouse full-field ERG were the STR components.
Literature
1.
go back to reference Frishman LJ (2006) Origins of the electroretinogram. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision, 2nd edn. The MIT Press, Cambridge, pp 139–183 Frishman LJ (2006) Origins of the electroretinogram. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision, 2nd edn. The MIT Press, Cambridge, pp 139–183
2.
go back to reference Bush RA, Sieving PA (1994) A proximal retinal component in the primate photopic ERG a-wave. Invest Ophthalmol Vis Sci 35:635–645PubMed Bush RA, Sieving PA (1994) A proximal retinal component in the primate photopic ERG a-wave. Invest Ophthalmol Vis Sci 35:635–645PubMed
3.
go back to reference Robson JG, Saszik SM, Ahmed J, Frishman LJ (2003) Rod and cone contributions to the a-wave of the electroretinogram of the macaque. J Physiol 547:509–530PubMedCentralPubMedCrossRef Robson JG, Saszik SM, Ahmed J, Frishman LJ (2003) Rod and cone contributions to the a-wave of the electroretinogram of the macaque. J Physiol 547:509–530PubMedCentralPubMedCrossRef
4.
go back to reference Robson JG, Frishman LJ (1998) Dissecting the dark-adapted electroretinogram. Doc Ophthalmol 95:187–215PubMedCrossRef Robson JG, Frishman LJ (1998) Dissecting the dark-adapted electroretinogram. Doc Ophthalmol 95:187–215PubMedCrossRef
5.
go back to reference Jamison JA, Bush RA, Lei B, Sieving PA (2001) Characterization of the rod photoresponse isolated from the dark-adapted primate ERG. Vis Neurosci 18:445–455PubMedCrossRef Jamison JA, Bush RA, Lei B, Sieving PA (2001) Characterization of the rod photoresponse isolated from the dark-adapted primate ERG. Vis Neurosci 18:445–455PubMedCrossRef
6.
go back to reference Friedburg C, Allen CP, Mason PJ, Lamb TD (2004) Contribution of cone photoreceptors and post-receptoral mechanisms to the human photopic electroretinogram. J Physiol 556:819–834PubMedCentralPubMedCrossRef Friedburg C, Allen CP, Mason PJ, Lamb TD (2004) Contribution of cone photoreceptors and post-receptoral mechanisms to the human photopic electroretinogram. J Physiol 556:819–834PubMedCentralPubMedCrossRef
7.
go back to reference Smith BJ, Tremblay F, Côté PD (2013) Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABAc receptors. Exp Eye Res 116:279–290 Smith BJ, Tremblay F, Côté PD (2013) Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABAc receptors. Exp Eye Res 116:279–290
9.
go back to reference Dang TM, Tsai TI, Vingrys AJ, Bui BV (2011) Post-receptoral contributions to the rat scotopic electroretinogram a-wave. Doc Ophthalmol 122:149–156PubMedCrossRef Dang TM, Tsai TI, Vingrys AJ, Bui BV (2011) Post-receptoral contributions to the rat scotopic electroretinogram a-wave. Doc Ophthalmol 122:149–156PubMedCrossRef
10.
go back to reference Alarcón-Martínez L, Avilés-Trigueros M, Galindo-Romero C et al (2010) ERG changes in albino and pigmented mice after optic nerve transection. Vis Res 50:2176–2187PubMedCrossRef Alarcón-Martínez L, Avilés-Trigueros M, Galindo-Romero C et al (2010) ERG changes in albino and pigmented mice after optic nerve transection. Vis Res 50:2176–2187PubMedCrossRef
11.
go back to reference Heiduschka P, Julien S, Schuettauf F, Schnichels S (2010) Loss of retinal function in aged DBA/2 J mice—new insights into retinal neurodegeneration. Exp Eye Res 91:779–783PubMedCrossRef Heiduschka P, Julien S, Schuettauf F, Schnichels S (2010) Loss of retinal function in aged DBA/2 J mice—new insights into retinal neurodegeneration. Exp Eye Res 91:779–783PubMedCrossRef
12.
go back to reference Harazny J, Scholz M, Buder T et al (2009) Electrophysiological deficits in the retina of the DBA/2 J mouse. Doc Ophthalmol 119:181–197PubMedCrossRef Harazny J, Scholz M, Buder T et al (2009) Electrophysiological deficits in the retina of the DBA/2 J mouse. Doc Ophthalmol 119:181–197PubMedCrossRef
13.
go back to reference Grozdanic SD, Betts DM, Sakaguchi DS et al (2003) Laser-induced mouse model of chronic ocular hypertension. Invest Ophthalmol Vis Sci 44:4337–4346PubMedCrossRef Grozdanic SD, Betts DM, Sakaguchi DS et al (2003) Laser-induced mouse model of chronic ocular hypertension. Invest Ophthalmol Vis Sci 44:4337–4346PubMedCrossRef
14.
go back to reference Brzezinski JA, Brown NL, Tanikawa A et al (2005) Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice. Invest Ophthalmol Vis Sci 46:2540–2551PubMedCentralPubMedCrossRef Brzezinski JA, Brown NL, Tanikawa A et al (2005) Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice. Invest Ophthalmol Vis Sci 46:2540–2551PubMedCentralPubMedCrossRef
15.
go back to reference Yuki K, Yoshida T, Miyake S et al (2013) Neuroprotective role of superoxide dismutase 1 in retinal ganglion cells and inner nuclear layer cells against N-methyl-d-aspartate-induced cytotoxicity. Exp Eye Res 115:230–238PubMedCrossRef Yuki K, Yoshida T, Miyake S et al (2013) Neuroprotective role of superoxide dismutase 1 in retinal ganglion cells and inner nuclear layer cells against N-methyl-d-aspartate-induced cytotoxicity. Exp Eye Res 115:230–238PubMedCrossRef
16.
go back to reference Ohno Y, Nakanishi T, Umigai N et al (2012) Oral administration of crocetin prevents inner retinal damage induced by N-methyl-d-aspartate in mice. Eur J Pharmacol 690:84–89PubMedCrossRef Ohno Y, Nakanishi T, Umigai N et al (2012) Oral administration of crocetin prevents inner retinal damage induced by N-methyl-d-aspartate in mice. Eur J Pharmacol 690:84–89PubMedCrossRef
17.
go back to reference Germain F, Istillarte M, Gómez-Vicente V et al (2012) Electroretinographic and histologic study of mouse retina after optic nerve section: a comparison between wild type and rd1 mice. Clin Exp Ophthalmol 41:593–602CrossRef Germain F, Istillarte M, Gómez-Vicente V et al (2012) Electroretinographic and histologic study of mouse retina after optic nerve section: a comparison between wild type and rd1 mice. Clin Exp Ophthalmol 41:593–602CrossRef
18.
go back to reference Heiduschka P, Schnichels S, Fuhrmann N et al (2010) Electrophysiological and histologic assessment of retinal ganglion cell fate in a mouse model for OPA1-associated autosomal dominant optic atrophy. Invest Ophthalmol Vis Sci 51:1424–1431PubMedCrossRef Heiduschka P, Schnichels S, Fuhrmann N et al (2010) Electrophysiological and histologic assessment of retinal ganglion cell fate in a mouse model for OPA1-associated autosomal dominant optic atrophy. Invest Ophthalmol Vis Sci 51:1424–1431PubMedCrossRef
19.
go back to reference Alavi MV, Bette S, Schimpf S et al (2007) A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy. Brain 130:1029–1042PubMedCrossRef Alavi MV, Bette S, Schimpf S et al (2007) A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy. Brain 130:1029–1042PubMedCrossRef
20.
go back to reference Alarcón-Martínez L, la Villa De P, Avilés-Trigueros M et al (2009) Short and long term axotomy-induced ERG changes in albino and pigmented rats. Mol Vis 15:2373–2383PubMedCentralPubMed Alarcón-Martínez L, la Villa De P, Avilés-Trigueros M et al (2009) Short and long term axotomy-induced ERG changes in albino and pigmented rats. Mol Vis 15:2373–2383PubMedCentralPubMed
22.
go back to reference Mojumder DK, Sherry DM, Frishman LJ (2008) Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram. J Physiol 586:2551–2580PubMedCentralPubMedCrossRef Mojumder DK, Sherry DM, Frishman LJ (2008) Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram. J Physiol 586:2551–2580PubMedCentralPubMedCrossRef
23.
go back to reference Gargini C, Bisti S, Demontis GC et al (2004) Electroretinogram changes associated with retinal upregulation of trophic factors: observations following optic nerve section. Neuroscience 126:775–783PubMedCrossRef Gargini C, Bisti S, Demontis GC et al (2004) Electroretinogram changes associated with retinal upregulation of trophic factors: observations following optic nerve section. Neuroscience 126:775–783PubMedCrossRef
24.
25.
go back to reference Ha Y, Saul A, Tawfik A et al (2011) Late-onset inner retinal dysfunction in mice lacking sigma receptor 1 (σR1). Invest Ophthalmol Vis Sci 52:7749–7760PubMedCentralPubMedCrossRef Ha Y, Saul A, Tawfik A et al (2011) Late-onset inner retinal dysfunction in mice lacking sigma receptor 1 (σR1). Invest Ophthalmol Vis Sci 52:7749–7760PubMedCentralPubMedCrossRef
26.
go back to reference Holcombe DJ, Lengefeld N, Gole GA, Barnett NL (2008) Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model. Br J Ophthalmol 92:683–688PubMedCrossRef Holcombe DJ, Lengefeld N, Gole GA, Barnett NL (2008) Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model. Br J Ophthalmol 92:683–688PubMedCrossRef
27.
go back to reference Viswanathan S, Frishman LJ, Robson JG et al (1999) The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136PubMed Viswanathan S, Frishman LJ, Robson JG et al (1999) The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136PubMed
28.
go back to reference Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the photopic negative response in patients with optic nerve atrophy. Arch Ophthalmol 122:341–346PubMedCrossRef Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the photopic negative response in patients with optic nerve atrophy. Arch Ophthalmol 122:341–346PubMedCrossRef
29.
go back to reference Rangaswamy NV, Frishman LJ, Dorotheo EU et al (2004) Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina. Invest Ophthalmol Vis Sci 45:3827–3837PubMedCrossRef Rangaswamy NV, Frishman LJ, Dorotheo EU et al (2004) Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina. Invest Ophthalmol Vis Sci 45:3827–3837PubMedCrossRef
30.
go back to reference Viswanathan S, Frishman LJ, Robson JG, Walters JW (2001) The photopic negative response of the flash electroretinogram in primary open angle glaucoma. Invest Ophthalmol Vis Sci 42:514–522PubMed Viswanathan S, Frishman LJ, Robson JG, Walters JW (2001) The photopic negative response of the flash electroretinogram in primary open angle glaucoma. Invest Ophthalmol Vis Sci 42:514–522PubMed
31.
go back to reference Niyadurupola N, Luu CD, Nguyen DQ et al (2013) Intraocular pressure lowering is associated with an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes. Invest Ophthalmol Vis Sci 54:1913–1919PubMedCrossRef Niyadurupola N, Luu CD, Nguyen DQ et al (2013) Intraocular pressure lowering is associated with an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes. Invest Ophthalmol Vis Sci 54:1913–1919PubMedCrossRef
33.
go back to reference Chrysostomou V, Crowston JG (2013) The photopic negative response of the mouse electroretinogram: reduction by acute elevation of intraocular pressure. Invest Ophthalmol Vis Sci 54:4691–4697PubMedCrossRef Chrysostomou V, Crowston JG (2013) The photopic negative response of the mouse electroretinogram: reduction by acute elevation of intraocular pressure. Invest Ophthalmol Vis Sci 54:4691–4697PubMedCrossRef
34.
go back to reference Li B, Barnes GE, Holt WF (2005) The decline of the photopic negative response (PhNR) in the rat after optic nerve transection. Doc Ophthalmol 111:23–31PubMedCrossRef Li B, Barnes GE, Holt WF (2005) The decline of the photopic negative response (PhNR) in the rat after optic nerve transection. Doc Ophthalmol 111:23–31PubMedCrossRef
36.
go back to reference Kaplan HJ, Chiang C, Chen J, Song S (2010) Vitreous volume of the mouse measured by quantitative high-resolution MRI. Annual meeting of the association for research in vision and ophthalmology (ARVO) E-abstract No. 4414 Kaplan HJ, Chiang C, Chen J, Song S (2010) Vitreous volume of the mouse measured by quantitative high-resolution MRI. Annual meeting of the association for research in vision and ophthalmology (ARVO) E-abstract No. 4414
37.
go back to reference Lei B, Yao G, Zhang K et al (2006) Study of rod- and cone-driven oscillatory potentials in mice. Invest Ophthalmol Vis Sci 47:2732–2738PubMedCrossRef Lei B, Yao G, Zhang K et al (2006) Study of rod- and cone-driven oscillatory potentials in mice. Invest Ophthalmol Vis Sci 47:2732–2738PubMedCrossRef
38.
go back to reference Jaissle GB, May CA, Reinhard J et al (2001) Evaluation of the rhodopsin knockout mouse as a model of pure cone function. Invest Ophthalmol Vis Sci 42:506–513PubMed Jaissle GB, May CA, Reinhard J et al (2001) Evaluation of the rhodopsin knockout mouse as a model of pure cone function. Invest Ophthalmol Vis Sci 42:506–513PubMed
39.
go back to reference Tanimoto N, Sothilingam V, Euler T et al (2012) BK channels mediate pathway-specific modulation of visual signals in the in vivo mouse retina. J Neurosci 32:4861–4866PubMedCrossRef Tanimoto N, Sothilingam V, Euler T et al (2012) BK channels mediate pathway-specific modulation of visual signals in the in vivo mouse retina. J Neurosci 32:4861–4866PubMedCrossRef
40.
go back to reference Salinas-Navarro M, Alarcón-Martínez L, Valiente-Soriano FJ et al (2009) Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice. Mol Vis 15:2578–2598PubMedCentralPubMed Salinas-Navarro M, Alarcón-Martínez L, Valiente-Soriano FJ et al (2009) Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice. Mol Vis 15:2578–2598PubMedCentralPubMed
41.
go back to reference Cuenca N, Pinilla I, Fernández-Sánchez L et al (2010) Changes in the inner and outer retinal layers after acute increase of the intraocular pressure in adult albino Swiss mice. Exp Eye Res 91:273–285PubMedCrossRef Cuenca N, Pinilla I, Fernández-Sánchez L et al (2010) Changes in the inner and outer retinal layers after acute increase of the intraocular pressure in adult albino Swiss mice. Exp Eye Res 91:273–285PubMedCrossRef
42.
go back to reference Blanco R, Germain F, Velasco A, Villa PDL (2002) Down-regulation of glutamate-induced conductances of retinal horizontal cells after ganglion cell axotomy. Exp Eye Res 75:209–216PubMedCrossRef Blanco R, Germain F, Velasco A, Villa PDL (2002) Down-regulation of glutamate-induced conductances of retinal horizontal cells after ganglion cell axotomy. Exp Eye Res 75:209–216PubMedCrossRef
43.
go back to reference Germain F, Blanco R, la Villa De P (2006) Expression and Functionality of gaba and glutamate receptors in axotomized ganglion cells of the rabbit retina. Annual meeting of the association for research in vision and ophthalmology (ARVO) E-abstract No. 160 Germain F, Blanco R, la Villa De P (2006) Expression and Functionality of gaba and glutamate receptors in axotomized ganglion cells of the rabbit retina. Annual meeting of the association for research in vision and ophthalmology (ARVO) E-abstract No. 160
44.
go back to reference Germain F, Fernández E, De la Villa P (2003) Morphometrical analysis of dendritic arborization in axotomized retinal ganglion cells. Eur J Neurosci 18:1103–1109PubMedCrossRef Germain F, Fernández E, De la Villa P (2003) Morphometrical analysis of dendritic arborization in axotomized retinal ganglion cells. Eur J Neurosci 18:1103–1109PubMedCrossRef
45.
go back to reference Kielczewski JL, Pease ME, Quigley HA (2005) The effect of experimental glaucoma and optic nerve transection on amacrine cells in the rat retina. Invest Ophthalmol Vis Sci 46:3188–3196PubMedCentralPubMedCrossRef Kielczewski JL, Pease ME, Quigley HA (2005) The effect of experimental glaucoma and optic nerve transection on amacrine cells in the rat retina. Invest Ophthalmol Vis Sci 46:3188–3196PubMedCentralPubMedCrossRef
46.
go back to reference Agudo M, Pérez-Marín MC, Lönngren U et al (2008) Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush. Mol Vis 14:1050–1063PubMedCentralPubMed Agudo M, Pérez-Marín MC, Lönngren U et al (2008) Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush. Mol Vis 14:1050–1063PubMedCentralPubMed
47.
go back to reference Chauhan BC, Pan J, Archibald ML et al (2002) Effect of intraocular pressure on optic disc topography, electroretinography, and axonal loss in a chronic pressure-induced rat model of optic nerve damage. Invest Ophthalmol Vis Sci 43:2969–2976PubMed Chauhan BC, Pan J, Archibald ML et al (2002) Effect of intraocular pressure on optic disc topography, electroretinography, and axonal loss in a chronic pressure-induced rat model of optic nerve damage. Invest Ophthalmol Vis Sci 43:2969–2976PubMed
48.
go back to reference Kong YX, Crowston JG, Vingrys AJ et al (2009) Functional changes in the retina during and after acute intraocular pressure elevation in mice. Invest Ophthalmol Vis Sci 50:5732–5740PubMedCrossRef Kong YX, Crowston JG, Vingrys AJ et al (2009) Functional changes in the retina during and after acute intraocular pressure elevation in mice. Invest Ophthalmol Vis Sci 50:5732–5740PubMedCrossRef
49.
50.
go back to reference Kenyon GT, Travis BJ, Theiler J et al (2004) Stimulus-specific oscillations in a retinal model. IEEE Trans Neural Netw 15:1083–1091PubMedCrossRef Kenyon GT, Travis BJ, Theiler J et al (2004) Stimulus-specific oscillations in a retinal model. IEEE Trans Neural Netw 15:1083–1091PubMedCrossRef
51.
go back to reference Neuenschwander S, Singer W (1996) Long-range synchronization of oscillatory light responses in the cat retina and lateral geniculate nucleus. Nature 379:728–732PubMedCrossRef Neuenschwander S, Singer W (1996) Long-range synchronization of oscillatory light responses in the cat retina and lateral geniculate nucleus. Nature 379:728–732PubMedCrossRef
53.
go back to reference Barnard AR, Charbel Issa P, Perganta G et al (2011) Specific deficits in visual electrophysiology in a mouse model of dominant optic atrophy. Exp Eye Res 93:771–777PubMedCrossRef Barnard AR, Charbel Issa P, Perganta G et al (2011) Specific deficits in visual electrophysiology in a mouse model of dominant optic atrophy. Exp Eye Res 93:771–777PubMedCrossRef
54.
go back to reference Machida S, Raz-Prag D, Fariss RN et al (2008) Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration. Invest Ophthalmol Vis Sci 49:442–452PubMedCrossRef Machida S, Raz-Prag D, Fariss RN et al (2008) Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration. Invest Ophthalmol Vis Sci 49:442–452PubMedCrossRef
55.
go back to reference Gunn DJ, Gole GA, Barnett NL (2011) Specific amacrine cell changes in an induced mouse model of glaucoma. Clin Exp Ophthalmol 39:555–563CrossRef Gunn DJ, Gole GA, Barnett NL (2011) Specific amacrine cell changes in an induced mouse model of glaucoma. Clin Exp Ophthalmol 39:555–563CrossRef
Metadata
Title
Contribution of retinal ganglion cells to the mouse electroretinogram
Authors
Benjamin J. Smith
Xu Wang
Balwantray C. Chauhan
Patrice D. Côté
François Tremblay
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Documenta Ophthalmologica / Issue 3/2014
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-014-9433-2

Other articles of this Issue 3/2014

Documenta Ophthalmologica 3/2014 Go to the issue